Association of Apolipoprotein E gene polymorphism with the risk of T2DM and obesity among Egyptian subjects.

BACKGROUND: Numerous reports investigated the involvement of apolipoprotein E (APOE) polymorphisms with elevated risk of type 2 diabetes mellitus (T2DM) and obesity. The principal objective of this study is to assess the contribution of APOE polymorphisms (rs429358 and rs7412) with the risk of T2DM and obesity. SUBJECTS AND METHODS: This work was designed involving 400 participants [100 healthy controls, 100 T2DM patients, 100 obese patients, and 100 T2DM + obese patients]. Genomic deoxyribonucleic acid (DNA) of the APOE polymorphisms was characterized using the PCR-RFLP assay. RESULTS: The common predominant genotype of the study population is the APOE Ɛ3/Ɛ3 [T2DM patients (46%), obese patients (52%), T2DM + obese patients (37%), and healthy controls (58%)]. The frequencies of the APOE Ɛ4/Ɛ4 genotype and the APOE*Ɛ4 allele were significantly elevated among T2DM patients (p-value < 0.05). Additionally, the frequencies of the APOE Ɛ2/Ɛ2 genotype and the APOE*Ɛ2 allele were significantly increased among obese patients (p-value < 0.05). Moreover, the frequencies of the APOE Ɛ2/Ɛ2 genotype, APOE*Ɛ2 allele, APOE Ɛ4/Ɛ4 genotype, and APOE*Ɛ4 allele were statistically significant among T2DM + obese patients (p-value < 0.05). CONCLUSIONS: APOE*Ɛ2 and APOE*Ɛ4 alleles were considered as independent risk factor among T2DM + obese patients. Furthermore, the APOE*Ɛ2 allele was correlated with elevated risk of obesity, while the APOE*Ɛ4 allele was correlated with elevated risk of T2DM.

Budget impact analysis for dapagliflozin in type 2 diabetes in Egypt.

Introduction: Type 2 diabetes mellitus (T2DM) is a major health problem in Egypt with a high impact on morbidity, mortality, and healthcare resources. This study evaluated the budget impact and the long-term consequences of dapagliflozin versus other conventional medications, as monotherapy, from both the societal and health insurance perspectives in Egypt.Methods: A static budget impact model was developed to estimate the financial consequences of adopting dapagliflozin on the healthcare payer budget. We measured the direct medical costs of dapagliflozin (new scenario) as monotherapy, compared to metformin, insulin, sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, and repaglinide (old scenarios) over a time horizon of 3 years. Myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), and initiation of renal replacement therapy (RRT) rates were captured from DECLARE TIMI 58 trial. One-way sensitivity analyses were conducted.Results: The budget impact model estimated 2,053,908 patients eligible for treatment with dapagliflozin from a societal perspective and 1,207,698 patients from the health insurance (HI) perspective. The new scenario allows for an initial savings of EGP121 million in the first year, which increased to EGP243 and EGP365 million in the second and third years, respectively. The total cumulative savings from a societal perspective were estimated at EGP731 million. Dapagliflozin allows for savings of EGP71, EGP143, and EGP215 million in the first, second and third years respectively, from the HI perspective, with total cumulative savings of EGP430 million over the 3 years.Conclusion: Treating T2DM patients using dapagliflozin instead of conventional medications, maximizes patients' benefits and decreases total costs due to drug cost offsets from fewer cardiovascular and renal events. The adoption of dapagliflozin is a budget-saving treatment option, resulting in substantial population-level health gains due to reduced event rate and cost savings from the perspective of the national healthcare system.

Safety and metabolic impact of Ramadan fasting in children and adolescents with type 1 diabetes.

BACKGROUND: Annually, many children and adolescents with type 1 diabetes mellitus (T1DM) insist on fasting for Ramadan despite being exempted and despite knowing all the risks. We aimed to assess the safety and metabolic impact of Ramadan fasting in children with T1DM using different insulin regimens. METHODS: Children with T1DM who choose to fast during Ramadan 1434/2013 (29 days) were recruited 3 months before Ramadan. They received pre-Ramadan intensive education. Three insulin regimens were included; Regimen-I (regular insulin/NPH); Regimen-II (regular insulin/insulin glargine) and Regimen-III (premixed insulin). Changes in weight, insulin dose, HbA1c, fructosamine and lipid profile were evaluated. RESULTS: Out of total 53 patients (24 male), 28 patients (52.8%) completed Ramadan fasting (fasting group). The remaining 25 patients were included in (broke-fasting group). Positive correlation between fructosamine changes and number of days fasted during Ramadan. Significant decrease in post-Ramadan fructosamine (<0.001) and increase in post-Ramadan total cholesterol and low density lipoprotein (LDL) levels were detected within fasting, broke-fasting and insulin regimen groups. Significant higher blood glucose at three time points, pre-Iftar, pre-Sohur and midday in Regimen-I compared to Regimen-II and Regimen-III (p=0.004). CONCLUSIONS: Fasting during Ramadan is feasible and is associated with significant improvement in fructosamine level in children with T1DM using different insulin regimens. Mandatory consideration to the quality and quantity of food offered to patients with T1DM during Ramadan to guard against adverse changes in lipid profile.

Leptin gene tetranucleotide repeat polymorphism in obese individuals in Egypt.

BACKGROUND: Leptin is a peptide hormone secreted by the adipose tissue. Genetic mutations of the leptin gene were reported to cause severe obesity. OBJECTIVES: This study was undertaken to investigate the association of the polymorphic tetranucleotide repeat locus 3' UTR of leptin gene with obesity in Egyptian cases. SUBJECTS AND METHODS: This study has included 120 subjects affected with obesity 57 of them were consistent with the diagnosis of metabolic syndrome (MS) while the rest (63) had simple obesity. These cases were compared to 83 normal weight healthy controls. All participants were subjected to an estimation of their body mass index (BMI), waist hip ratio (WHR), serum as well as characterization of leptin gene tetranucleotide repeat (TTTC)n polymorphism by PCR technique. RESULTS: Thirteen different alleles were identified in all cases of obesity versus only 5 alleles in normal controls. The most frequent allele was the 154 bp allele (57.5% in all cases of obesity vs. 92.2% in controls). Total cases with obesity showed a significantly higher carriage rate of class II alleles (I/II + II/II genotypes) compared to healthy controls (48.3% vs. 6.0%, OR=14.6, 95% CI=5.5-38.6, p=<0.0001). This was more apparent in the group with simple obesity (52.3% vs. 6.0%, OR=17.2, 95% CI=6.1-48.1, p=<0.0001) than in MS cases (43.9 % vs. 6.0 %, OR =12.19, 95% CI=4.9-30.4, p=< 0.0001). Interestingly, cases with MS did not differ from those with simple obesity regarding their class I or II allele frequencies (p> 0.05). Although serum lipids were significantly higher in obese cases compared to controls, no difference was found among obese cases with different leptin gene class genotypes (p> 0.05). CONCLUSIONS: Tetranucleotide repeat (TTTC)n polymorphism in the 3' UTR of the human leptin gene was associated with obesity in Egyptian obese cases showing higher class II allele carriage rate. However, the lipoprotein levels were not affected by this polymorphism.

Does laparoscopic ovarian diathermy change clomiphene-resistant PCOS into clomiphene-sensitive?

PURPOSE: To test the role of laparoscopic ovarian diathermy (LOD) in improving the ovarian response to clomiphene citrate (CC) in clomiphene-resistant polycystic ovary syndrome (PCOS) patients. METHODS: The study comprised of 234 CC-resistant PCOS women who were treated with LOD. Eighty-four patients that remained anovulatory after LOD received 100-150 mg CC for 5 days starting from day 3 of induced menstruation for 1-3 cycles. Outcome measures were; ovulation, pregnancy, miscarriage and live birth rates. RESULTS: Ovulation occurred in 80/162 cycles (49.4%) and in 30/84 patients (35.7%). Pregnancy occurred in 13/84 patients (15.5%) and in 13/80 cycles (16.2%). Miscarriage and live birth rates were 23.1 and 76.9%, respectively. Ovulatory women showed significantly lower baseline BMI (P < 0.001), Ferriman-Gallwey score (P = 0.02), testosterone (P = 0.03), higher sex hormone binding globulin and lower free androgen index (P < 0.001) compared with anovulatory women. The baseline fasting insulin was statistically significantly lower and fasting glucose:insulin ratio was statistically significantly higher (P = 0.003, 0.002) in ovulatory compared with anovulatory patients. CONCLUSIONS: LOD improves the ovarian response to CC in at least one-third of CC-resistant patients who remained anovulatory following LOD especially in women who are less hyperandrogenic and less insulin resistant.

Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial.

AIM: To compare the effect of combined metformin-clomiphene citrate (CC) with highly purified urinary FSH (HP-uFSH) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS). METHODS: One-hundred fifty-three anovulatory women with CC-resistant PCOS were selected in this randomised controlled trial. Patients received combined metformin-CC (n=75, 205 cycles) or HP-uFSH (n=78, 186 cycles) for three cycles. Outcome measures were; Ovulation rate, number of growing and mature follicles, serum E2, serum P, endometrial thickness, pregnancy and miscarriage rates. RESULTS: The ovulation rate per cycle was significantly higher in the HP-uFSH group (83.8% vs. 62%, p=0.01). The number of follicles ≥ 12 mm ≥ 14 mm and ≥ 18 mm on the hCG day was significantly greater in the HP-uFSH group (p=0.01, p=0.02 and p=0.03, respectively). Pregnancy occurred in 23/205 cycles (11.2%) in combined metformin-CC group and 40/186 cycles (21.5%) in the HP-uFSH group; the difference was statistically significant (p=0.02). Two patients in the HP-uFSH group suffered mild OHSS. CONCLUSIONS: Combined metformin-CC resulted in modest ovulation and pregnancy rates without side effects. It is logical to offer this first for CC-resistant PCOS women before resorting to more expensive alternatives especially in developing communities where economic aspects of therapy are important.

Effect of genetic polymorphisms on the development of secondary failure to sulfonylurea in egyptian patients with type 2 diabetes.

OBJECTIVE: This study investigated the possibility that genetic factors, such as polymorphism of K inward rectifier subunit (Kir6.2), E23K, and Arg(972) polymorphism of insulin receptor sub-strate-1 (IRS-1), may predispose patients to sulfonylurea failure. METHODS: A total of 100 unrelated Egyptian patients with type 2 diabetes were recruited. They were divided into two equal groups: group I consisted of patients with secondary failure to sulfonylurea (hemoglobin A(1c) ≥ 8% despite sulfonylurea therapy) while group II consisted of patients whose condition was controlled with oral therapy. RESULTS: Of all the patients, 45% and 14% were carriers of the K allele and Arg(972) variants respectively. The frequency of the K allele was 34% among patients with diabetes that was controlled with oral therapy and 56% among patients with secondary failure to sulfonylurea. The frequency of the Arg(972) IRS-1 variant was 6% among patients with diabetes controlled with oral therapy and 22% among patients with secondary failure. CONCLUSION: The E23K variant of the Kir6.2 gene and Arg(972) IRS-1 variants are associated with increased risk for secondary failure to sulfonylurea.